Transplanted Cells May Hold the Key to Curing

The Einstein team, led by Dr. Sanjeev Gupta, cured hemophilia A by transplanting healthy liver endothelial cells from donor mice into a mouse model of the disease. In curing these mice, the Einstein researchers also overturned conventional wisdom regarding which cells produce factor VIII, the crucial clotting protein that is lacking in people with type A hemophilia.

“It was assumed that factor VIII was made by the hepatocytes—cells that perform many of the liver’s functions and comprise most of its bulk. But our research had suggested that the primary sources were special endothelial cells that line the sinusoids, the liver’s blood-filled spaces. We did this study to confirm the role of liver endothelial cells in producing factor VIII and to see if transplanting them from a healthy donor liver could correct hemophilia A in an animal model.”

The donor mice had been genetically engineered so that their endothelial cells expressed the gene for green fluorescent protein. This allowed the researchers to see whether the liver endothelial cells could successfully engraft within the recipients’ livers. Before transplantation, to “make room” for the donated cells to engraft and proliferate, the researchers gave recipient mice a dose of the toxic chemical monocrotaline to deplete their native liver endothelial cells.

“Three months after transplantation, when we examined the livers of recipient mice, we found that the transplanted cells had engrafted and increased in number,” says Dr. Antonia Follenzi, lead author of the study. “Even more important, those mice with the most transplanted cells in their livers produced factor VIII in sufficient amounts to completely correct their hemophilia A.” The principle established by this study might also help in treating hemophilia B and, more broadly, aid in “tissue engineering” in the many other areas of the body where endothelial cells are found, says Dr. Gupta.